Inhibition op ascorbic acid (AA) accumulation by dietary flavonoids in human CACO-2 cells

AA and flavonoids are commonly co-present in plant food. We used Caco-2 human intestinal cells as a model to study their interaction in the intestine. The intracellular accumulation of [14C]-AA was found to be Na-dependent, and inhibited by flavonoids, quercetin (Q) and genistein (G), dose-dependently. Oxidation of AA may partly account for the effect of Q as we found AA stabilized Q probably by self-degradation. No chemical interaction between AA and G was observed. Inhibition of Nadependent AA transporter can not explain the effect as the inhibitory potency of Q (50 pM) over 20 min was 27±2 vs. 21±3 % of control, Na vs. Na-free, respectively. Q and G probably did not inhibit AA accumulation through their known property of kinase inhibition since other modulators of protein kinase A, C, or proteintyrosine kinase did not affect AA accumulation in the expected direction. Flavonoids were known to interfere with the function of MDR (an efflux pump found in Caco-2 cells). Substrates of MDR, including nifedipine, verapamil, vinblastin, vincristine, 17-estradiol and diethylstilbestrol, all reduced AA accumulation. The inhibitory effects of G (20/tM), nifedipine (20 pM) and diethylstilbestrol (10 jtMX75±2,76±4, and 63±3 % of control, individually) were additive only to 42±3 % of control. Our observation suggests that cellular net AA accumulation may depend on the action of MDR.